The major objective of this work is to determine the nature and capabilities of the human atypical lymphocyte. The study focuses on atypical cells in the context of Epstein-Barr virus (EBV) induced infectious mononucleosis (IM). It seeks to determine the mechanisms of generation of the cells, their characteristics, their role in disease and their relevance to control of potentially malignant lymphoproliferation. An in vitro model has been established in which peripheral leukocytes from EBV seropositive and seronegative donors are stimulated with inactivated virus. Cytotoxic blast cells are generated in cultures of immune leukoctyes. We propose to examine the relationship of the blasts to natural killer cells and compare their cytotoxic specificity with those of atypical lymphocytes generated in vivo in IM. Single cell assays will be used to accomplish this. We also intend to determine the contribution of the EBV receptor to the uniquely vigorous immune response represented by the atypical cells. Generation of cytotoxicity by EBV antigens alone will be compared with that induced by antigen coupled with the receptor. The effects of virus binding to the receptor on B-cell activation and subsequent interface with regulatory T cells will also be examined.